Effect of hexachlorobenzene on haem synthesis

Abstract

Several drugs are known to induce the liver microsomal mixed-function oxidase system when administered in vivo or even in vitro in cell culture. A sequence of events has been suggested in which the drug is visualized to induce δ-aminolaevulinate synthetase, the first and rate-limiting enzyme of the haem-biosynthetic pathway, which is followed by enhanced haem synthesis and cytochrome P-450 content, facilitating the increase in the drug-metabolizing activity of the liver microsomal fraction. The present studies show that the fungicide hexachlorobenzene, when administered to female rats, can lead to enhanced amounts and rate of synthesis of cytochrome P-450 under conditions when the rate of total haem synthesis has not appreciably altered. The subsequent increase in the rate of total haem synthesis as well as the initial increase in amounts of cytochrome P-450 are brought about under conditions when δ-aminolaevulinate synthetase activity remains constant. However, manifestation of porphyria due to prolonged drug administration is accompanied by a twofold increase in δ-aminolaevulinate synthetase activity. The increase in enzyme activity appears to be due to a decreased degradation rate of the enzyme.